Method for promoting ovulation, parturition, and lactation in mammals

ABSTRACT

The present invention generally relates to various methods for promoting ovulation, parturition and lactation in female mammals. These benefits are obtained by administering to the mammals a composition containing a D 2  receptor antagonist that does not substantially cross the blood brain barrier. In one embodiment, the D 2  receptor antagonist is domperidone. The domperidone can be administered to the mammal either orally or subcutaneously and can be used to treat, for instance, anestrous mammals, mammals that have problems bearing offspring and mammals suffering from agalactia. Unexpectedly, it has also been discovered that the D 2  receptor antagonist may also stimulate feed intake, causing the mammal to eat more and gain weight faster.

FIELD OF THE INVENTION

[0001] The present invention generally relates to a method for promotingovulation, parturition and lactation in female mammals. Moreparticularly, the present invention is directed to a method ofadministering a dopamine D₂ receptor antagonist, such as domperidone, toa female mammal for altering hormonal levels in the animal in order topromote ovulation, parturition or lactation.

BACKGROUND OF THE INVENTION

[0002] Breeders of various animals, such as horses and other livestock,face many problems in getting the animals to breed properly. Forinstance, some female mammals fail to ovulate and fall into heat inregular intervals. Mammals that exhibit a prolonged period of inactivitybetween two periods of heat are described as being anestrous. Anestrousfemale mammals will not accept the male and are incapable of conceivingoffspring.

[0003] Another problem breeders experience is the inability of somemammals to prepare for and give birth after the mammals have becomepregnant and the fetus is ready to be born. In preparation for andduring the act of giving birth, a process known as parturition, thepregnant mammal should experience cervical relaxation, swelling of thevulva, and relaxation of ligaments around the pelvis. Without theseevents occurring, the mammal is not capable of giving natural,unassisted birth. Further, should these events not occur, the health ofthe mother and of the unborn offspring are at grave risk.

[0004] Another problem commonly experienced by breeders is the inabilityof mammals to produce and secrete milk after giving birth. The conditionof failing to lactate properly after child birth is referred to asagalactia, and is especially prevalent in mares and other livestock.Should the mammal not lactate properly, the offspring must then bebottle fed which is time consuming, labor intensive, and significantlyadds to the cost of raising the livestock.

[0005] Each of the problems mentioned above can be caused to a greatextent by hormonal imbalance or by hormonal irregularities. Hormonesreleased in the body are primarily responsible for initiating ovulation,parturition, and lactation in mammals. Thus, if hormones are notreleased in the body at particular critical times, the above describedproblems can be experienced.

[0006] For instance, hormones can be prevented from being released inthe body by various chemical agents. One such known chemical agent isdopamine. Dopamine is a decarboxylated form of dopa and is found andproduced in the adrenal glands of mammals. Dopamine is believed to beproduced by the body when it is necessary to suppress hormone secretion.Dopamine suppresses hormone release by binding to and tying up receptorson the anterior pituitary, an endocrine gland located at the base of thebrain not far from the hypothalamus. By binding to the anteriorpituitary, the gland is prevented from receiving a stimulus hormone thatcauses it to release other hormones such as those necessary forovulation, parturition, and lactation.

[0007] Although dopamine is necessary during particular periods forkeeping hormone levels in the body within controlled ranges, excesslevels of dopamine can adversely interfere with the process ofreproduction. Also, besides dopamine, there are other chemical agentsthat can interfere with or prevent hormone secretion, adverselyaffecting biological processes.

[0008] Thus, a need exists for a method of promoting follicular growthand ovulation, parturition, and lactation in female mammals. A need alsoexists for treating anestrous mammals, agalactic mammals, and mammalsthat fail to prepare for parturition when a fetus is ready to be born. Afurther need exists for a chemical agent that antagonizes dopamine andother chemicals that act in a similar manner in order to counteracthormonal imbalance and irregularities.

SUMMARY OF THE INVENTION

[0009] The present invention recognizes and addresses the foregoingdisadvantages, and others of prior art constructions and methods.

[0010] Accordingly, it is an object of the present invention to providea process for promoting ovulation and for treating anestrous mammals.

[0011] Another object of the present invention is to provide a methodfor promoting parturition in a pregnant mammal that is at the end of thepregnancy cycle.

[0012] It is another object of the present invention to provide aprocess for promoting lactation and for treating agalactia in mammalsthat have just given birth.

[0013] Still another object of the present invention is to provide aprocess for controlling hormonal release in the body.

[0014] Another object of the present invention is to provide a methodfor altering hormone levels in the body of a mammal by administering tothe mammal a dopamine antagonist.

[0015] It is another object of the present invention to provide aprocess for treating a mammal that has excess levels of dopamine andother similar acting agents within its body.

[0016] These and other objects of the present invention are achieved byproviding a method for promoting follicular growth and ovulation, forpreparing a mammal for parturition, and for promoting lactation byadministering to a female mammal a composition. The composition containsa dopamine D₂ receptor antagonist. For instance, in one embodiment, thecomposition can contain domperidone.

[0017] The present inventor has used domperidone in the past fortreating animals suffering from fescue toxicosis. For instance, thepresent inventor's prior work is disclosed in U.S. Pat. No. 5,372,818entitled “Method of Treating Fescue Toxicosis with Domperidone”, whichis incorporated herein by reference in its entirety. In U.S. Pat. No.5,372,818, it was discovered not only that domperidone is an effectiveagent for treating fescue toxicosis, but that domperidone does notsubstantially cross the blood brain barrier. Therefore, domperidone canbe administered to animals while avoiding substantial adverse behavioraland neurological side effects. Such neuroleptic side effects have beenobserved in animals exposed to other D₂ receptor antagonists such as thedrugs, metoclopramide and sulpiride.

[0018] Although U.S. Pat. No. 5,372,818 provides great advances in theart for treating animals infected with fescue toxicosis, variousadvantages, aspects and features of the present invention remain absentfrom the present inventor's prior patent.

[0019] According to the present invention, ovulation, parturition orlactation can be promoted by administering to a mammal a compositioncontaining a dopamine D₂ receptor antagonist, such as domperidone. TheD₂ receptor antagonist can be administered to the mammal in an amountfrom about 0.08 mg to about 3.3 mg per kilogram of body weight of themammal. The D₂ receptor antagonist can be administered to the mammaleither orally or subcutaneously.

[0020] Specifically, when using domperidone to promote follicular growthand ovulation, domperidone can be orally administered at a concentrationof from about 0.2 mg to about 3.3 mg per kilogram weight of said mammal.In one preferred embodiment, the dosage of domperidone is about 0.55 mgper kilogram weight of the mammal.

[0021] When administered subcutaneously, the dosage can be from about0.08 mg to about 1.32 mg and particularly around 0.22 mg per kilogramweight of the mammal.

[0022] When attempting to promote parturition, udder development, andlactation, on the other hand, domperidone can be administered orally toa mammal at a dosage of from about 0.2 mg to about 3.3 mg andparticularly at about 1.1 mg per kilogram weight of the mammal. Whenadministered subcutaneously, the dosage of domperidone can be from about0.08 mg to about 1.32 mg and particularly at about 0.44 mg per kilogramweight of the mammal.

[0023] All of the above dosage levels according to the present inventioncan be given daily. Although unknown, it is believed that the treatmentscause hormonal levels in the mammal to change for promoting eitherovulation, parturition or lactation. Unexpectedly, it has also beendiscovered that a dopamine D₂ receptor antagonist such as domperidonemay also cause an increase in feed intake in the mammal resulting inweight increases.

[0024] Other objects, features and aspects of the present invention arediscussed in greater detail below.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0025] It is to be understood by one of ordinary skill in the art thatthe present discussion is a description of exemplary embodiments only,and is not intended as limiting the broader aspects of the presentinvention, which broader aspects are embodied in the exemplaryconstruction.

[0026] The present invention is generally directed to various processesand methods for promoting and stimulating follicular growth andovulation, for preparing a mammal for parturition, and for promoting andstimulating udder development and lactation. The process of the presentinvention can be used to treat anestrous mammals, agalactic mammals, andmore generally any mammal experiencing problems during the reproductivecycle. The process of the present invention can also be used tomanipulate and control ovulation and lactation. For instance, in mammalsthat only ovulate seasonally, the present invention can be used topromote ovulation at times when ovulation would not normally occur.

[0027] In general, the objects and advantages of the present inventionare achieved by administering to a female mammal a compositioncontaining a dopamine D₂ receptor antagonist. A D₂ receptor antagonistshould be chosen but does not substantially cross the blood brainbarrier in order to ensure that the mammal does not suffer any adversebehavioral or neurological side effects. For instance, in a preferredembodiment, the dopamine D₂ receptor antagonist is domperidone.

[0028] Although unknown, it is believed that domperidone ties upreceptor cells in the anterior pituitary and other places in the bodypreventing various chemical agents, such as dopamine, from binding tothe receptor cells and altering the release of hormones throughout thebody. By altering the effects of dopamine and other similar agents,domperidone allows the anterior pituitary and other glands of the bodyto secrete hormones necessary for ovulation, parturition, and lactationas will be described in greater detail hereinafter.

[0029] As discussed above, one embodiment of the present invention isdirected to a process for stimulating and promoting follicular growthand ovulation. The process can be used to treat anestrous mammals, tocause a mammal to ovulate out of season, or to otherwise control whenovulation occurs.

[0030] The process of the present invention can be used to treat anymammal, but is particularly applicable to livestock. For instance, manyproblems have been experienced in attempting to get horses to breed.Further, mares only ovulate and fall into heat during particular timesof the year. The process of the present invention cannot only be used totreat horses that experience problems ovulating but can also be used tobreed horses during times of the year when it was not before possible.

[0031] According to the present invention, follicular growth andovulation is promoted by administering to a mammal a dopamine D₂receptor antagonist. In one preferred embodiment, the dopamine D₂receptor antagonist is domperidone. The D₂ receptor antagonist can betaken orally by the mammal or can be injected subcutaneously.

[0032] In one embodiment, when using domperidone, it has been found thatovulation is promoted when the domperidone is taken orally by a mammalin an amount from about 0.2 mg/kg (mg of domperidone per kg of bodyweight) to about 3.3 mg/kg. At concentrations greater than 3.3 mg/kg, nofurther benefits have been observed. Thus far, the best results havebeen obtained when domperidone has been taken orally at a concentrationof about 0.55 mg/kg.

[0033] If the domperidone is injected subcutaneously into the mammal,the dosages listed above can be reduced to about 40% of the oral dose.Thus, if injected into a mammal, domperidone can be administered at aconcentration of from about 0.08 mg/kg to about 1.32 mg/kg, with apreferred concentration of about 0.22 mg/kg.

[0034] Ovulation is the process by which an egg is discharged from afollicle of an ovary and is released into the fallopian tube and theuterus. More particularly, in mammals, as eggs mature in the ovary, theeggs are surrounded by a layer of follicular cells creating a fluidfilled follicle. As the egg reaches maturity, the fluid filled folliclebulges from the surface of the ovary. Stimulated by a hormone, ovulationoccurs when the follicle ruptures, releasing the egg.

[0035] Ovarian cycles are initiated and controlled by a variety ofhormones secreted throughout the body. Specifically, these hormonesinclude follicle stimulating hormone (FSH) which is secreted by thepituitary gland and which stimulates follicular and egg growth.Luteinizing hormone (LH), which is also released from the pituitarygland, stimulates the follicle to secrete estrogen which causes thewalls of the uterine to thicken. LH also triggers ovulation causing thefollicle to rupture.

[0036] The levels and frequency of release of these hormones can bealtered in the body by various chemical agents such as dopamine.Although unknown, it is believed that the D₂ receptor antagonists of thepresent invention, such as domperidone, neutralize the effects ofdopamine and other related chemical agents. By administering to a mammala D₂ receptor antagonist, LH and FSH can be released by the body withoutinhibition causing ovulation to occur.

[0037] Besides promoting ovulation, the present invention is alsodirected to a process for preparing a mammal for parturition. Thisprocess is for treating mammals and particularly livestock that haveproblems giving birth once pregnant.

[0038] Parturition is stimulated in a mammal according to the presentinvention by administering to the mammal a composition containing adopamine D₂ receptor antagonist. For instance, in one embodiment, thecomposition can contain domperidone. Once administered to the mammal, itis believed that the composition neutralizes the effects of dopamine andother similar chemical agents from altering the release of hormones thatprepare a mammal for giving birth. Thus, the composition of the presentinvention allows the body to secrete hormones that may affect cervicaldilation and general broodiness.

[0039] By administering the composition to pregnant mammals, the mammalis more likely to give birth on time. The composition also promotesnatural births and prevents against having to deliver the offspring byC-sections. The treatment not only protects the unborn offspring duringdelivery but also protects the pregnant mother from being harmed duringbirth.

[0040] In order to promote normal parturition, in one embodiment, apregnant mammal can be orally fed domperidone at a concentration of fromabout 0.2 mg/kg of body weight to about 3.3 mg/kg. In one preferredembodiment, the oral dosage can be about 1.1 mg/kg.

[0041] When injected subcutaneously into the mammal, domperidone hasbeen found to produce effective results at concentrations of from about0.08 mg/kg to about 1.32 mg/kg, with best results being obtained atabout 0.44 mg/kg. Amounts greater than 1.32 mg/kg can be administered tothe animal without any adverse side effects. Additional benefits,however, have not been observed at higher dosage levels.

[0042] Whether administered orally or subcutaneously, treatments of theD₂ receptor antagonist administered to the mammal can begin at any timeduring the pregnancy. For larger livestock such as cattle and horses,the treatment should begin about fifteen to twenty days prior to theexpected birth date.

[0043] A further embodiment of the present invention is directed to aprocess for promoting udder development and lactation in female mammals.The process can be used to prevent or treat agalactia or any otherailments regarding the low level or non-production of milk. Forinstance, lactation problems have been particularly observed in maresthat have recently given birth. After giving birth, many mares eitherfail to produce milk or do not produce enough milk to adequately nurturethe foal. When this occurs, the foal must be bottle fed or fed in someother manner which significantly adds to the expense of raising thelivestock.

[0044] The process of the present invention can be used in thesecircumstances to stimulate or increase milk production in non-milkingmares and other mammals. Further, the process can be used simply toincrease milk production without any adverse effects. For instance, theprocess of the present invention can also be used to increase thequantity of milk obtained from cows for human consumption.

[0045] Lactation is stimulated and promoted according to the presentinvention by administering to mammals a composition containing adopamine D₂ receptor antagonist. For instance, the composition cancontain domperidone in an amount sufficient to stimulate milkproduction.

[0046] In one embodiment, milk production was stimulated in horses byorally administering to the horses domperidone in a concentration offrom about 0.2 mg/kg of body weight to about 3.3 mg/kg of body weight,and particularly at a concentration of about 1.1 mg/kg. At oral dosagesgreater than 3.3 mg/kg, no further beneficial results were observed.

[0047] Domperidone can also be administered to the animalsubcutaneously. If injected into the mammal, about 40% of the dosageamounts given above can be used. Thus, when injected subcutaneously, thedomperidone concentration can be from about 0.08 mg/kg to about 1.32mg/kg.

[0048] Although unknown, it is believed that the dopamine D₂ receptorantagonist, such as domperidone, influences hormonal levels within theanimal. Domperidone is believed to alter hormone levels by neutralizingthe effect of dopamine-like agents that prevent particular hormones frombeing secreted. With respect to lactation, it is believed that thedopamine D₂ receptor antagonist increases the levels of progesterone,estrogen and prolactin within the body of the mammal. These hormones arebelieved to be primarily responsible for promoting udder development andlactation.

[0049] Besides promoting ovulation, preparing a mammal for parturition,and stimulating lactation, it has also been unexpectedly discovered thatthe composition of the present invention can cause a mammal to increaseits feed intake and thus gain weight faster. This process isparticularly beneficial in raising livestock for human consumption.

[0050] In order to increase feed intake according to the presentinvention, a dopamine D₂ receptor antagonist, such as domperidone, isadministered to a mammal. The treatment can be given to the mammalorally or subcutaneously. If domperidone is used and administeredorally, the domperidone should be fed to the mammal at a concentrationof from about 0.2 mg/kg of body weight to about 3.3 mg/kg of body weightand particularly at about 1.1 mg/kg. If domperidone is injected into themammal, the dosage should be from about 0.08 mg/kg to about 1.32 mg/kg.

[0051] At the present time, it is unknown why domperidone causesincreases in feed intake. It is believed, however, that domperidone maystimulate feed intake by increasing levels of the hormone prolactin inthe body of the mammal. It may also be possible that domperidone causeslevels of hormones to be altered that firm up the gut of the mammal. Ifthe muscles of the gut were to be stimulated, then food passage mayincrease in the gut allowing the animal to eat more.

[0052] In general, in delivering an effective dosage of a dopamine D₂receptor antagonist to a mammal according to the present invention,various vehicles may be used. For instance, when taken orally, the D₂receptor antagonist may be combined with a feed or feed supplementmaterial as the carrier. If injected, the drug may be mixed with anysuitable carrier. Additionally, the D₂ receptor antagonist, such asdomperidone, may be added to salt blocks or mineral blocks duringcasting or mixed directly into feed. Further, various otheradministration techniques well known in the art may be employed. It isto be understood that the present invention is not to be limited to anyparticular vehicle.

[0053] It also should be appreciated that although the above descriptionand following examples relate primarily to livestock such as horses andcattle, it is believed that the drug will work as described with anymammal. For instance, although untested at the present time, it isbelieved that a dopamine D₂ receptor antagonist that does notsubstantially cross the blood brain barrier such as domperidone may beadministered to humans for promoting ovulation, facilitating childbirth,or stimulating lactation.

[0054] The present invention may be better understood with reference tothe following examples.

EXAMPLE NO. 1

[0055] The following tests were performed in order to demonstrate theability of domperidone to stimulate and promote ovulation in mares.

[0056] Ten mares were fed a composition containing domperidone at aconcentration of 0.55 mg/kg of body weight. The composition wasadministered daily. Specifically, the domperidone was mixed withmolasses and fed to the mares with a 5 cc syringe. Nine additional mareswere used as a control. These mares were fed the molasses carrier notcontaining any domperidone.

[0057] Of importance, the treatments were carried out in January andFebruary during a time when mares typically do not ovulate. Thefollowing results were obtained: TABLE 1 Effect of Domperidone onFollicular Growth and Ovulation No. of Days Treated with No. of ofTreatment Test Domperidone Days of Date of Before No. at .55 mg/kgTreatment Ovulation Ovulation 1 No 45 d/n ovulate d/n ovulate 2 No 45d/n ovulate d/n ovulate 3 No 45 d/n ovulate d/n ovulate 4 No 25 Feb. 2625 5 No 45 d/n ovulate d/n ovulate 6 No 45 d/n ovulate d/n ovulate 7 No45 d/n ovulate d/n ovulate 8 No 37 Mar. 10 37 9 No 45 d/n ovulate d/novulate 10 Yes 18 Feb. 9  18 11 Yes 15 Feb. 6  18 12 Yes 21 Feb. 12 2113 Yes 17 Feb. 8  17 14 Yes 24 Feb. 15 24 15 Yes 14 Feb. 5  14 16 Yes 16Feb. 7  16 17 Yes 22 Feb. 13 22 18 Yes 45 d/n ovulate d/n ovulate 19 Yes19 Feb. 10 19

[0058] As shown above, only two of the control mares ovulated. Incomparison, nine of the ten mares treated with domperidone ovulated.Also of significance, the treated mares ovulated during the early partof February. No neurological side effects were observed in any of themares treated with domperidone during the study.

EXAMPLE NO. 2

[0059] The following tests were performed to demonstrate the ability ofdomperidone to prepare a mammal for parturition and to stimulate udderdevelopment and lactation.

[0060] Twelve known agalactic mares who were either pregnant or had justgiven birth were treated with domperidone. The domperidone wasadministered orally at a dosage of 1.1 mg/kg of body weight per day. Allof the mares treated were not suffering from fescue toxicosis. Thefollowing results were obtained: TABLE 2 Effect of Domperidone onPreparation for Parturition, Udder Development and Lactation In MaresDays Before (−) Days Before (−) Was Mare or After Expected or AfterExpected Mare's Udder Mare's Udder Lactating Did Mare Foaling Dosing WasFoaling that Development Before Development After Normally Have A TestNo. Initiated Mare Foaled Treatment Began Treatment Began After Foaling?Live Foal? 1  +5 +12  Very Little Dripping Milk 5th Day Yes Yes ofTreatment 2 −28 −1 Very Little Increased Weekly Yes Yes 3 No data +8 NoDevelopment After 2 Days, Made Yes Yes Udder Sack 4  +6 +15  Very LittleDeveloped Slowly But Yes Yes Natural 5  +4 +14  Virtually No UdderDeveloped Adequately No. but drug Yes helped some 6 −21  0 Normal NormalYes Yes 7  +5 No data Incomplete Small Udder Developed As Yes Yes UdderSoon As Treatment Started 8 −24 −3 No Development Very Slight Yes YesDevelopment 9 No data +3 Minimal Gradual Development Yes Yes 10  −13 Nodata Slight Base; No Filling Normal Development Yes Yes of Teat 11  −20−3 No Development No Response Yes Yes 12  −10 −2 None to MinimalImmediate Yes Yes Development After Treatment

EXAMPLE NO. 3

[0061] It has also been unexpectedly discovered that treating a mammalwith a D₂ receptor antagonist, such as domperidone, increases feedintake. The following results demonstrate this phenomenon.

[0062] Ten quarter horse mares were housed in individual pens and fed astandard feed concentrate weighing 0.5% of each mares' initial bodyweight at approximately 8:00 A.M. each day during the study. Inaddition, hay was fed to the mare ad libitum each day. During the night,the mares were placed in a dry lot having no access to food.

[0063] After seven days on the above feed schedule (control), the mareswere orally fed at 8:00 A.M. each day domperidone at a dosage of 1.1mg/kg of body weight. The domperidone was fed to the mares in a molassescarrier. During treatment with domperidone, the mares were fed theconcentrate feed and hay in the same manner as during the controlperiod. Domperidone was fed to the mares for two weeks. The followingresults were obtained: TABLE 3 Effect of Domperidone On The Daily FeedIntake of Mares Avg. Hay Avg. Hay Initial Consumption Consumption BodyBefore After Mare Weight Concentrate Treatment Treatment ID (lbs) Feed(lbs) (lbs) (lbs) 1 1025 5.1 11.2 13.0 2  980 4.9 10.3 12.2 3 1110 5.612.2 14.1 4  900 4.5 11.1 13.2 5 1050 5.3 12.0 14.1 6 1000 5.0 11.0 14.27  980 4.9  9.8 12.3 8 1010 5.1 11.0 13.5 9 1100 5.5 12.5 15.0 10   9504.8 10.2 12.1

[0064] As shown above, daily hay consumption increased for each of theten mares after treatment with domperidone began.

[0065] These and other modifications and variations to the presentinvention may be practiced by those of ordinary skill in the art,without departing from the spirit and scope of the present invention,which is more particularly set forth in the appended claims. Inaddition, it should be understood that aspects of the variousembodiments may be interchanged both in whole or in part. Furthermore,those of ordinary skill in the art will appreciate that the foregoingdescription is by way of example only, and is not intended to limit theinvention so further described in such appended claims.

What is claimed:
 1. A method for promoting follicular growth andovulation in mammals comprising the step of: administering to a femalemammal a composition comprising a dopamine D₂ receptor antagonist thatdoes not substantially cross the blood brain barrier, said dopamine D₂receptor antagonist being administered to said female mammal in anamount sufficient to promote follicular growth and ovulation.
 2. Amethod as defined in claim 1 , wherein said dopamine D₂ receptorantagonist comprises domperidone.
 3. A method as defined in claim 1 ,wherein said dopamine D₂ receptor antagonist is administered to saidfemale mammal in an amount from about 0.08 mg to about 3.3 mg perkilogram weight of said mammal.
 4. A method as defined in claim 1 ,wherein said composition is administered orally.
 5. A method as definedin claim 1 , wherein said composition is administered subcutaneously. 6.A method as defined in claim 2 , wherein said domperidone isadministered to said female mammal orally in an amount from about 0.2 mgto about 3.3 mg per kilogram weight of said mammal.
 7. A method asdefined in claim 2 , wherein said domperidone is administered to saidfemale mammal subcutaneously in an amount from about 0.08 mg to about1.32 mg per kilogram weight of said mammal.
 8. A method as defined inclaim 1 , wherein said female mammal is an animal selected from thegroup consisting of a mare, or a cow.
 9. A method for promotingparturition in mammals comprising the step of: administering to a femalemammal a composition comprising a dopamine D₂ receptor antagonist thatdoes not substantially cross the blood brain barrier, said dopamine D₂receptor antagonist being administered to said pregnant mammal in anamount sufficient to promote parturition.
 10. A method as defined inclaim 9 , wherein said dopamine D₂ receptor antagonist comprisesdomperidone.
 11. A method as defined in claim 9 , wherein said dopamineD₂ receptor antagonist is administered to said pregnant mammal in anamount from about 0.08 mg to about 3.3 mg per kilogram weight of saidmammal.
 12. A method as defined in claim 9 , wherein said composition isadministered orally.
 13. A method as defined in claim 9 , wherein saidcomposition is administered subcutaneously.
 14. A method as defined inclaim 10 , wherein said composition is administered orally to saidpregnant mammal in an amount from about 0.2 mg to about 3.3 mg perkilogram weight of said mammal.
 15. A method as defined in claim 10 ,wherein said composition is administered subcutaneously to said pregnantmammal in an amount from about 0.08 mg to about 1.32 mg per kilogramweight of said mammal.
 16. A method as defined in claim 9 , wherein saidpregnant mammal is an animal selected from the group consisting of amare or a cow.
 17. A method for promoting lactation in mammalscomprising the step of: administering to a female mammal a compositioncomprising a dopamine D₂ receptor antagonist that does not substantiallycross the blood brain barrier, said dopamine D₂ receptor antagonistbeing administered to said female mammal in an amount sufficient topromote lactation.
 18. A method as defined in claim 17 , wherein saiddopamine D₂ receptor antagonist comprises domperidone.
 19. A method asdefined in claim 17 , wherein said dopamine D₂ receptor antagonist isadministered to said female mammal in an amount from about 0.08 mg toabout 3.3 mg per kilogram weight of said mammal.
 20. A method as definedin claim 17 , wherein said composition is administered orally.
 21. Amethod as defined in claim 17 , wherein said composition is administeredsubcutaneously.
 22. A method as defined in claim 18 , wherein saiddomperidone is administered orally to said female mammal in an amountfrom about 0.2 mg to about 3.3 mg per kilogram weight of said mammal.23. A method as defined in claim 18 , wherein said domperidone isadministered subcutaneously to said female mammal in an amount fromabout 0.08 mg to about 1.32 mg per kilogram weight of said mammal.
 24. Amethod as defined in claim 17 , wherein said female mammal is an animalselected from the group consisting of a mare and a cow.
 25. A method foradjusting hormonal levels in female mammals in order to promoteovulation, parturition or lactation comprising the step of:administering to a female mammal a composition comprising domperidone,said domperidone being administered to said female mammal in an amountfrom about 0.08 mg to about 3.3 mg per kilogram weight of said femalemammal.